Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.4.1 (phosphodiesterase)
18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Theophylline and 3-isobutyl-1-methylxanthine, two cyclic nucleotide phosphodiesterase inhibitors, when fed to wild-type Drosophila adults, cause the rapid decay of learning index after training in a shock-odor learning paradigm. The drugs practically do not affect the olfactory acuity of flies, hence they influence the learning/memory process itself. The time courses of memory decay resemble those of the memory mutants rutabaga and amnesiac and, to a lesser extent, dunce2 and dunceM11. Theophylline further deteriorates the learning performance of dunceM11. Biochemical characterization of the inhibition of the two major phosphodiesterase isoenzymes in Drosophila by theophylline predicts only a slight inhibition of these enzymes in vivo, in accordance with the unchanged level of cAMP in wild-type fly heads during drug feeding. 8-Phenyltheophylline, an adenosine receptor antagonist in mammals, slightly retards memory decay in the wild-type. It is suggested that alkylxanthines induce memory decay in Drosophila by interfering with cAMP dynamics at more than one point of its metabolism.
...
PMID:On the pharmacological phenocopying of memory mutations in Drosophila: alkylxanthines accelerate memory decay. 172 65

On the ultrastructural level, the role of Ca2+ and cAMP in the rat spermatogenesis was studied. Using a K-pyroantimonate method for intracellular localization of Ca2+, precipitates were found within (i) the vesicular component of the chromatoid body, (ii) vesicular elements of the trans-Golgi area including coated vesicles, (iii) smooth endoplasmic reticulum vesicles and cisterns accompanying the perinuclear (manchette) microtubules, and (iv) mid-piece mitochondria of germ and Sertoli cells. The results suggest a close relationship between the Ca(2+)-containing smooth endoplasmic reticulum and the control of microtubule assembly within microdomains. Theophylline (a cAMP-phosphodiesterase inhibitor) treatment of rats (96 mg/kg daily i.p. over 5 days) caused a significant increase of (a) the GERL-related coated vesicles and (b) the number of manchette microtubules.
...
PMID:Role of Ca2+ and cAMP in rat spermatogenesis--ultrastructural evidences. 172 28

1. Voltage-clamp recording of Ca(2+)-activated chloride currents in Xenopus oocytes was used to study the effects of caffeine on the liberation of intracellular Ca2+ induced by photo-release of inositol 1,4,5-trisphosphate (InsP3) from caged InsP3. Bath application of caffeine, at concentrations between 0.1 and 10 mM, reduced or abolished the current evoked by photo-release of InsP3 and by microinjection of InsP3. 2. Caffeine did not appreciably reduce currents evoked by injection of Ca2+ into oocytes, whereas measurements using the Ca2+ indicator Rhod-2 showed that it instead inhibited the liberation of Ca2+ by InsP3. 3. Caffeine increased the threshold amount of InsP3 required to evoke a current response and proportionally reduced the currents evoked by suprathreshold levels of InsP3. 4. Theophylline and 3-isobutyl-1-methylxanthine (IBMX) were much less potent than caffeine, and few changes were seen in the InsP3 responses following application of forskolin or intracellular injection of cyclic AMP. Thus, inhibition of InsP3 responses by caffeine does not arise through inhibition of phosphodiesterase enzymes. 5. Even at high (10 mM) concentrations, caffeine did not itself elicit any clear Ca(2+)-activated current. It is therefore unlikely that inhibition of the InsP3 responses arise because caffeine itself liberates Ca2+ from intracellular stores. 6. The site of action of caffeine is intracellular, because injections of caffeine into the oocyte strongly inhibited responses to InsP3, whereas local extracellular applications of similar amounts were almost without effect.
...
PMID:Caffeine inhibits inositol trisphosphate-mediated liberation of intracellular calcium in Xenopus oocytes. 184 13

The action of theophylline on phasic tension and slow inward current (Isi) was investigated on isolated voltaged-clamped frog atrial fibres. The action of theophylline was both dose- and time-dependent; the most effective dose was 2.10(-3)M. Theophylline induced a rapid positive inotropic effect which cannot be attributed to a beta-adrenoceptor stimulation or to an adenosine antagonism; this effect was closely related to an increase in slow inward current (Isi), probably due to an inhibition of phosphodiesterase activity and a subsequent increase in cAMP content. The decline of the positive inotropic effect of theophylline was discussed in terms of additional effects of the drug. Theophylline, consistently with its phosphodiesterase inhibitory action, was shown to potentiate the effects of isoprenaline on phasic tension and Isi; however no potentiation was observed after reserpine-induced depletion of endogenous catecholamines. It might be thought that non-specific effects of reserpine on some steps of cardiac excitation-contraction coupling counteract the effects of theophylline.
...
PMID:Theophylline effects on phasic tension and slow inward current of isolated frog atrial fibres: influence on the action of isoprenaline. 186 90

Atrial natriuretic factor administered in the large dose did not change glomerular filtration rate, but it was diuretic in low-sodium rats. In response to ANF, excretion of c-GMP was decreased in low-sodium rats in comparison with normal-sodium stimulated c-GMP accumulation in isolated glomeruli was more diminished in low- than normal sodium rats. These results indicate that attenuated glomerular responses to ANF in low-sodium rats might be due to increase of plasma Angiotensin II (Ang II) level, which increases intracellular Ca++ concentration. Theophylline can potentiate the renal response to ANF. We suggest that Ca(++)-activated c-GMP phosphodiesterase plays a major role in the regulation of intracellular accumulation of c-GMP in glomeruli exposed to ANF.
...
PMID:Attenuated glomerular responses to atrial natriuretic factor in low-sodium rats is prevented by theophylline. 216 1

The free extracellular concentration of theophylline in the brain was estimated from microdialysis samples. Two different methods were used to estimate extracellular concentrations by microdialysis, the perfusion rate method and the difference method. Theophylline 20 mg/kg (s.c.) gave a sufficiently stable level of theophylline in the brain 60 min after injection and lasting over the observation period to allow application of the two methods in vivo. The relation between dose and dialysate concentration was linear. It was found that doses of 20-24 mg/kg theophylline corresponded to a free extracellular concentration of 60-90 microM. The behaviour of theophylline-treated rats was assessed in parallel experiments by means of a holeboard apparatus. Behavioural activation was observed in the dose-range 3-30 mg/kg. It is concluded that behavioural effects of theophylline can be induced at a concentration well below that required to inhibit phosphodiesterase but within the range in which adenosine receptor blockade may be observed, suggesting that the latter mechanism is responsible for the behavioural effects of theophylline.
...
PMID:Theophylline concentration in the extracellular space of the rat brain: measurement by microdialysis and relation to behaviour. 225 93

Avidin induction in chick tissues in vivo and in vitro was studied by a phosphodiesterase inhibitor, theophylline, and compared to progesterone-dependent induction. Theophylline (100 mg/kg, ip) caused a significant increase in avidin content only in the oviduct of diethylstilbestrol-treated chicks, but not in the lung, muscle, intestine, plasma, or in the bursa of Fabricius. Diethylstilbestrol priming was necessary for oviductal avidin induction in vivo by theophylline. In the oviduct culture, theophylline at a concentration between 100 and 500 micrograms/ml caused a dose-dependent increase in avidin production. Effects of theophylline and progesterone on avidin synthesis in oviduct culture were synergistic. Avidin production was dependent on protein and RNA synthesis, since induction was inhibited by cycloheximide and actinomycin D. Avidin induction by theophylline resembled progesterone-dependent induction, beginning 9 h after the injection in vivo and 12 h after administration of these drugs in vitro. Avidin induced by theophylline showed heat-induced biotin exchange identical to that of progesterone-induced avidin, indicating close similarity of these proteins. The results suggest that theophylline can mimic the action of progesterone on avidin production, and that cyclic nucleotides may have a role in the regulation of avidin synthesis.
...
PMID:Avidin induction by theophylline in vivo and in vitro. 242 18

Methylxanthines are primary agents used in treatment of hypersensitivity disease. Because polymorphonuclear leukocyte (PMN) activation is associated with generation of potent inflammatory mediators, xanthine effects on the PMN respiratory burst were studied. Enprofylline, a xanthine with important therapeutic potential, does not antagonize adenosine and was contrasted with theophylline. Although enprofylline was more potent at low concentrations, both drugs exhibited dose-dependent inhibition of PMN activation at concentrations greater than 10 mumol/L (1.8 micrograms/ml). Oxygen metabolite generation was decreased by 30% to 40% at therapeutic drug concentrations and by 85% at 1 mmol/L of theophylline. Inhibition by isoproterenol or prostaglandin E2 but not dibutyryl cAMP was potentiated by either xanthine. Isoproterenol effects were also increased when isoproterenol was evaluated in whole blood specimens obtained from subjects after a loading dose of aminophylline. Although these results were most compatible with cAMP phosphodiesterase inhibition, other commonly proposed mechanisms of methylxanthine activity were also studied. Theophylline but not enprofylline blocked adenosine inhibition of PMN activation. Neither xanthine shifted the calcium dose-response when PMNs were activated with calcium ionophore. Because oxygen metabolites generated by the FMN are mediators of inflammation and hypersensitivity, direct inhibition of PMN activation as well as potentiation of catecholamine activity may be important therapeutic effects of theophylline and enprofylline.
...
PMID:Therapeutic concentrations of theophylline and enprofylline potentiate catecholamine effects and inhibit leukocyte activation. 243 4

The influence of cyclic AMP on cartilage degradation was investigated by using phosphodiesterase inhibitors [theophylline and 3-isobutyl-1-methylxanthine (IBMX)], forskolin (which activates the catalytic subunit of adenylate cyclase) and cyclic AMP analogues (dibutyryl and 8-bromo). Breakdown was assessed by quantification of proteoglycans released into the media of 8-day bovine nasal-septum cartilage cultures. Theophylline (1-20 mM), IBMX (0.01-2 mM) and dibutyryl cyclic AMP (0.1-2 mM) had little or no influence on the rate of proteoglycan release from unstimulated (no-endotoxin) cartilages. A small but detectable increase in breakdown was observed with 8-bromo cyclic AMP (0.5-2 mM) and forskolin (50-75 micrograms/ml). To examine potential inhibitory influences of these agents, the cyclic AMP modulators were added to cultures simultaneously treated with Salmonella typhosa endotoxin (12-25 micrograms/ml), a potent stimulator of cartilage degradation. The 3-4-fold stimulation of breakdown by endotoxin was strikingly inhibited by all three classes of cyclic AMP regulators. Optimal inhibition was found at 10-20 mM-theophylline, 1-2 mM-IBMX, 50-75 micrograms of forskolin/ml, 2 mM-dibutyryl cyclic AMP and 2 mM-8-bromo cyclic AMP. Inhibition was shown to be reversible, indicating that cartilages were viable after treatment. Sepharose CL-2B chromatography of proteoglycan products released from treated cartilages showed that the endotoxin-stimulated shift to lower average Mr was significantly prevented by cyclic AMP analogues and phosphodiesterase inhibitors. Together, these results show that agents which increase cyclic AMP inhibit both quantitative and qualitative aspects of endotoxin-mediated cartilage degradation.
...
PMID:Cyclic AMP-regulating agents inhibit endotoxin-mediated cartilage degradation. 244 11

Milrinone and sulmazole, two recently developed drugs, inhibit specific fractions of the phosphodiesterase (PDE) isozyme system. Since theophylline aspecifically inhibits the PDE complex, we compared the effects of milrinone and sulmazole with those of theophylline on antigen-induced bronchoconstriction, vasoconstriction, mediator release and leukotriene production. In the isolated perfused and ventilated lung of actively sensitized rats, we elicited antigen-induced bronchoconstriction, vasoconstriction and release of mediators like histamine, 5-hydroxytryptamine (5-HT) and slow-reacting substance of anaphylaxis (SRS-A). Milrinone, sulmazole and theophylline inhibited antigen-induced bronchoconstriction and vasoconstriction in a dose-dependent manner with minor differences in potency. Antigen-induced release of preformed mediators like histamine and 5-HT was inhibited only at high concentrations of milrinone, whereas sulmazole failed to inhibit mediator release. Theophylline also failed to inhibit 5-HT release. However, SRS-A synthesis was markedly reduced by these drugs in relatively low concentrations. It is concluded that milrinone and sulmazole have anti-allergic effects similar to those of theophylline and that all three PDE inhibitors reduce SRS-A synthesis.
...
PMID:Anti-allergic effects of milrinone and sulmazole in isolated rat lungs in comparison with theophylline. 247 95


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---